Sample analyzer and computer program product

ABSTRACT

A sample analyzer including a detection unit for irradiating a biological sample with light and obtaining optical information; a cell classification processor for classifying cells contained in the biological sample into cell groups based on the optical information; a scattered light information obtaining processor for obtaining scattered light information relating to a cell included in a predetermined cell group; a calculation processor for calculating a component value corresponding to an amount of component contained in cell included in the predetermined cell group based on the scattered light information; and an output device for outputting the component value calculated by the calculation means is disclosed. A computer program product is also disclosed.

FIELD OF THE INVENTION

The present invention relates to a sample analyzer and computer programproduct, and specifically relates to a sample analyzer and computerprogram product for analyzing biological samples based on opticalinformation.

BACKGROUND

Analysis of biological samples such as blood and urine is used in thedifferentiation diagnosis and treatment of disease. Accordingly, bloodanalyzers which analyze blood using a flow cytometer have been developedfor automatic high-speed analysis of many biological samples (refer toU.S. Pat. No. 4,735,504, and No. 6,525,807).

Many useful clinical laboratory test items for the differentiation andtreatment of disease have been discovered in conjunction with medicaladvances in recent years. For example, the amount of hemoglobincontained in reticulocytes is used in the differentiation and treatmentof anemia. The blood analyzers disclosed in the patent publicationsabove are incapable of obtaining such information.

Non-patent literature has disclosed that parameters (RBC-Y and RET-Y)obtained from histograms of forward scattered light of erythrocytes andreticulocytes are respectively equivalent to the amount of hemoglobincontained in the erythrocytes and reticulocytes (for example, C. Briggs,R. Rogers, B. Tompson, S. J. Machin: New Red Cell Parameters on theSysmex XE-2100 as Potential Markers of functional Iron Deficiency;Sysmex Journal International; Vol. 11 No. 2:63-68).

Although these parameters correlate with the amount of hemoglobincontained in erythrocytes and reticulocytes, the non-patent literaturedoes not report an analyzer capable of obtaining the amount ofhemoglobin contained in erythrocytes and reticulocytes based on theseparameters and providing the analysis result to a user.

SUMMARY

The scope of the present invention is defined solely by the appendedclaims, and is not affected to any degree by the statements within thissummary.

An object of the present invention is to increase the number of usefulclinical laboratory test items which can be measured by an analyzer.

A first aspect of the present invention is a sample analyzer thatcomprises a detection unit for irradiating a biological sample withlight and obtaining optical information; a cell classification means forclassifying cells contained in the biological sample into cell groupsbased on the optical information; a scattered light informationobtaining means for obtaining scattered light information relating to acell included in a predetermined cell group; a calculation means forcalculating a component value corresponding to an amount of componentcontained in cell included in the predetermined cell group based on thescattered light information; and an output device for outputting thecomponent value calculated by the calculation means.

A second aspect of the present invention is a sample analyzer thatcomprises a detection unit for irradiating a blood sample with light andobtaining scattered light information and fluorescent light information;a cell classification means for classifying cells contained in the bloodsample into a plurality of cell groups including a reticulocyte groupbased on the scattered light information and fluorescent lightinformation obtained by the detection unit; a reticulocyte groupscattered light information obtaining means for obtaining reticulocytegroup scattered light information relating to a reticulocyte included inthe reticulocyte group; a calculation means for calculating an amount ofhemoglobin contained in the reticulocyte based on the reticulocyte groupscattered light information; and a display for displaying the amount ofhemoglobin calculated by the calculation means.

A third aspect of the present invention is a computer program productfor executing a method of analyzing a biological sample, the computerprogram product comprising computer program code for obtaining opticalinformation from a biological sample irradiated with light; computerprogram code for classifying cells contained in the biological sampleinto a plurality of cell groups based on the optical information;computer program code for obtaining scattered light information relatingto a cell included in a predetermined cell group; computer program codefor calculating a component value corresponding to an amount of acomponent contained in a cell included in the predetermined cell groupbased on the scattered light information; and computer program code foroutputting the calculated component value.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of the general structure of an embodimentof the sample analyzer of the present invention and peripheral devices;

FIG. 2 is a block diagram showing the internal structures of a devicebody 1 and data processing terminal 2;

FIG. 3 is a perspective view showing the structure of an opticaldetection unit 20;

FIG. 4 is a flow chart showing the process of analyzing reticulocytesand mature red blood cells;

FIG. 5 shows a scattergram 58 stored in the controller 26 on the mainbody side;

FIG. 6 shows a scattergram 58 stored in the controller 26 on the mainbody side;

FIG. 7 shows a scattergram 58 stored in the controller 26 on the mainbody side;

FIG. 8 shows a scattergram 58 stored in the controller 26 on the mainbody side;

FIG. 9 shows an analysis result screen 71 displayed on the display 16 onthe terminal side;

FIG. 10 shows an analysis result screen 71 displayed on the display 16on the terminal side; and

FIG. 11 shows a two-dimensional distribution diagram used for equationdetermination.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The preferred embodiments of the present invention are describedhereinafter with reference to the drawings.

The embodiments of the present invention are described below based onthe drawings.

An embodiment of the sample analyzer of the present invention is ahemocytometer for analyzing blood and calculating the number of whiteblood cells (WBC), red blood cells (RBC), and platelets (PLT) and thelike.

As shown in FIG. 1, the sample analyzer 10 of the present embodimentincludes a device body 1, and data processing terminal 2 connected tothe device body 1 through a communication cable (not shown in thedrawing).

The device body 1 is connected to a vacuum source 5 for supplyingpositive pressure and negative pressure to the device body 1 through atube (not shown in the drawing). The device body 1 is connected to asampler 6, which automatically transports specimen containers so as tosupply samples (blood) to the device body 1. The device body 1 isconnected through a tube to a reagent container not shown in thedrawing, and suctions reagent from the reagent container using thenegative pressure supplied from the vacuum source 5.

The device body 1 is provided with sample suction units 14 a and 14 bfor suctioning blood, a display 11 on the body side which includes aliquid crystal display, and an input unit 12 on the body side whichincludes a keyboard.

The sample suction unit 14 a is used in manual mode to suction bloodwhile the user holds the specimen container, and sample suction unit 14b is used in sampler mode using the sampler 6 to automatically transportsample containers and suction blood.

The data processing terminal 2 includes a terminal body 15, terminalside display 16 which includes a CRT display, and a terminal side inputunit 18 which includes a keyboard and mouse not shown in the drawing.

The data processing terminal 2 is connected, by respective communicationcables (not shown in the drawings), to a page printer 3 for printing alist of analysis results, a color graphics printer 4 for printingparticle distribution diagrams and scattergrams, and a data printer 7for printing analysis results on form paper.

As shown in FIG. 2, the device body 1 includes sample suction units 14 aand 14 b, sample preparation unit 17, detection section 19, A/Dconversion circuit 21, body side controller 26, body side display 11,body side input unit 12, and I/O interface 32 a.

The sample preparation unit 17 performs processing such as dilution,hemolysis, and staining by mixing the blood suctioned by the samplesuction units 14 a and 14 b and the reagent suction from a reagentcontainer not shown in the drawing. The assay sample prepared by theseprocesses is supplied to the detection section 19. The detection section19 includes an optical detection unit 20, electrical detection unit 22,and absorbance detection unit 24.

The electrical detection unit 22 includes a sensor using the RF/DCdetection method, and a sensor using the sheath flow DC detectionmethod. The sensor described as the ‘first measuring part’ in thespecification of U.S. Pat. No. 6,525,807 may be used as the sensor usingthe sheath flow DC detection method.

A detection unit including a transparent cell disposed medially to alight-emitting diode and a photoreceptor element may be used as theabsorbance detection unit 24. The absorbance detection unit 24 outputsan electric signal representing the transmission light intensity for adilution fluid alone, and an electric signal representing thetransmission light intensity of a hemoglobin assay sample to the A/Dconversion circuit 21. These electric signals are subjected to digitalconversion in the A/D conversion circuit 21, and are input to the bodyside controller 26.

The body side controller 26 is mainly a microcomputer which includes aCPU, ROM, RAM and the like. The body side controller 26 calculates theanalysis result from data output from the detection section 19 and inputthrough the A/D conversion circuit 21. For example, the body sidecontroller 26 calculates the hemoglobin (HGB) concentration from thedifference between the transmission light intensity (absorbance) outputfrom the absorbance detection unit 24 and input through the A/Dconversion circuit 21. Then, the body side controller 26 transmits thecalculated analysis result through the I/O interface 32 a to the dataprocessing terminal 2. The body side controller 26 stores theoperational expressions, described later, which were used in thecalculation of the analysis result.

The body side controller 26 controls the operation of the sample suctionunits 14 a and 14 b, sample preparation unit 17, detection section 19and the like. The body side controller 26 receives data input from thebody side input unit 12, and displays predetermined information on thebody side display 11. Examples of the information displayed on the bodyside display 11 include the main clinical laboratory test items of theanalysis results, error information and the like.

The terminal body 15 includes an I/O interface 32 b, and terminal sidecontroller 34. The I/O interfaces 32 a and 32 b are connected through acommunication cable 33.

The terminal side controller 34 includes a CPU, ROM, RAM, and hard diskand the like. The terminal side controller 34 displays analysis resultstransmitted from the device body 1 through the I/O interface 32 b on theterminal side display 16, and prints the data on the various printers(refer to FIG. 1).

The terminal side controller 34 transmits the data input from theterminal side input unit 18 to the device body 1 through the I/Ointerface 32 b.

As shown in FIG. 3, the optical detection unit 20 includes a nozzle 36,laser diode 40, collimator lens 42, sheath flow cell 43, condenser lens44, pinhole plate 45, photodiode 46, condenser lens 47, dichroic mirror48, photomultiplier tube 49, filter 50, pinhole plate 51,photomultiplier tube 52, and amps 53 through 55.

The assay sample supplied from the sample preparation unit 17 (refer toFIG. 2) flows from the nozzle 36 and through an orifice 38 of the sheathflow cell 43.

Light from the laser diode 40 irradiates the assay sample flowingthrough the orifice 38 of the sheath flow cell 43 through the collimatorlens 42. The light scattered in front of the assay sample flowingthrough the orifice 38 (forward scattered light) passes through thecondenser lens 44 and pinhole plate 45 and enters the photodiode 46.

The light scattered laterally from the assay sample flowing through theorifice 38 (lateral scattered light) enters the photomultiplier tube 49through the condenser lens 47 and dichroic mirror 48.

The fluorescent light emitted from the assay sample flowing through theorifice 38 (lateral fluorescent light) by the light emitted from thelaser diode 40 enters the photomultiplier tube 52 through the condenserlens 47, dichroic mirror 48, filter 50, and pinhole plate 51.

The photodiode 46 outputs an electrical signal which represents theintensity of the input forward scattered light (forward scattered lightintensity). The photomultiplier tube 49 outputs an electrical signalrepresenting the intensity of the input lateral scattered light (lateralscattered light intensity). The photomultiplier tube 52 outputs anelectrical signal representing the intensity of the input lateralfluorescent light (lateral fluorescent light intensity).

The electrical signals output from the photodiode 46, photomultipliertube 49, and photomultiplier tube 52 are amplified by the amps 53, 54,55, respectively, and are input to the A/D conversion circuit 21.

The operation of the sample analyzer of the present embodiment isbriefly described below with reference to FIGS. 1 through 10. When auser operates the body side input unit 12 or terminal side input unit 18to issue instructions to start an analysis operation, the sample suctionunit 14 a or 14 b performs a blood suctioning operation in accordancewith the selected operating mode. Then, the sample preparation unit 17prepares a predetermined assay sample, and the assay sample is suppliedto each detection unit of the detection section 19. The opticaldetection unit 20 respectively outputs electrical signals representingthe forward scatter light intensity, lateral scattered light intensity,and fluorescent light intensity to the A/D conversion circuit 21. Theelectrical detection unit 22 and absorbance detection unit 24 alsooutput electrical signals obtained by detecting the assay sample to theA/D conversion circuit 21. The A/D conversion circuit 21 digitallyconverts the electrical signals output from the detection section 19,and outputs the data to the body side controller 26. The body sidecontroller 26 analyzes the data and obtains analysis results for thevarious clinical laboratory test items. Then, the body side controller26 displays predetermined items from among the analysis results on thebody side display 11, and transmits all analysis results to the dataprocessing terminal 2. Then, the terminal side controller 34 of the dataprocessing terminal 2 displays the received analysis results on theterminal side display 16, and stores the analysis results.

The processes of analyzing reticulocytes (RET) and mature erythrocytesusing the optical detection unit 20 is described in greater detailbelow.

When analyzing reticulocytes (RET) and mature erythrocytes, the samplepreparation unit 17 dilutes the blood suctioned by the sample suctionunit 14 a or 14 b approximately 200 times, and stains the dilutedsolution using a predetermined stain. Consequently, a prepared assaysample is supplied to the optical detection unit 20. Then, the opticaldetection unit 20 irradiates the assay sample with light, and outputselectrical signals representing the forward scattered light intensity,lateral scattered light intensity, and lateral fluorescent lightintensity, respectively, to the A/D conversion circuit 21. The A/Dconversion circuit 21 subjects the electrical signal output from theoptical detection unit 20 to digital conversion, and outputs the data tothe body side controller 26. The body side controller 26 analyzes thereticulocytes and mature erythrocytes using the data representing theforward scattered light intensity and lateral fluorescent lightintensity among the data output from the A/D conversion circuit 21. Thereagents described in U.S. Pat. No. 5,821,127 may be employed as thereagents in the preparation of the sample.

The process of analyzing reticulocytes and mature erythrocytes performedby the body side controller 26 is described below using FIG. 4. Thisprocess is executed once with a predetermined timing for eachmeasurement of a single sample.

When the data representing the forward scattered light intensity,lateral scattered light intensity, and lateral fluorescent lightintensity is transmitted from the optical detection unit 20 and input tothe body side controller 26 through the A/D conversion circuit 21, then,the body side controller 26 acquires data in a predetermined period andstores the data representing the forward scattered light intensity andlateral fluorescent light intensity.

Then the body side controller 26 creates and stores a two dimensionaldiagram (scattergram) which has the forward scattered light intensity onthe vertical axis and the lateral fluorescent light intensity on thehorizontal axis based on the stored data representing the forwardscattered light intensity and lateral fluorescent light intensity (stepS2). The scattergram 58 stored by the body side controller 26 is shownin FIG. 5.

The scattergram 58 is created by extracting individual cells which passthrough the orifice 38 based on the data representing the forwardscattered light intensity and lateral fluorescent light intensity,determining the forward scattered light intensity and lateralfluorescent light intensity for each extracted cell, and plotting theforward scattered light intensity on the vertical axis and plotting thelateral fluorescent light intensity on the horizontal axis in atwo-dimensional diagram for all cells.

Next, the body side controller 26 classifies and stores the individuallyextracted cells in cell groups which include the mature erythrocytegroup 60, reticulocyte group 62, fragmented erythrocyte group 62, andplatelet group 64, as shown in FIG. 6 (step S3).

The mature erythrocyte group 60, reticulocyte group 62, and plateletgroup 64 can be created, for example, using the methods described in thespecifications of U.S. Pat. No. 5,006,986 and No. 5,117,357. Sincemature erythrocytes do not contain RNA within the cell, the obtainedlateral fluorescent light intensity is extremely low. Sincereticulocytes contain RNA within the cell, a comparatively high lateralfluorescent light intensity is obtained. Using these criteria, thesemethods classify cells which emit a lateral fluorescent light intensitygreater than a predetermined amount as reticulocytes. The scatteredlight intensity obtained by irradiating a cell with light reflects thesize of the cell. Since a platelet is smaller than both a matureerythrocyte and a reticulocyte, platelets can be classified separatelyfrom mature erythrocytes and reticulocytes.

The fragmented erythrocyte group 63 can be created using, for example,the method described in the specification of U.S. Patent Publication No.2001-53551.

The mature erythrocyte group 60, reticulocyte group 62, fragmentederythrocyte group 63, and platelet group 64 may have a fixed rangedetermined beforehand, or the ranges may be modified in accordance withthe cell incidence condition on the scattergram.

Next, the body side controller 26 creates and stores trisects thereticulocyte group 62 in accordance with the lateral fluorescent lightintensity, and creates and stores an LFR range 66, MFR range 68, and HFRrange 70 (step S4).

Since cells which have a high lateral fluorescent light intensity arecells which contain an abundance of RNA produce, it can be stated thatreticulocytes which have a high lateral fluorescent light intensity arejuvenile reticulocytes. That is, it can be said that reticulocytes inthe HFR range 70 are younger than reticulocytes in the MFR range 68, andreticulocytes in the MFR range 68 are younger than reticulocytes in theLFR range 66.

Next, the body side controller 26 calculates and stores the RET-Y andRBC-Y as scattered light information, as shown in FIG. 8 (step S5).

RET-Y is the average value of the forward scattered light intensities ofall cells (that is, reticulocytes) included in the reticulocyte group62.

RBC-Y is the average value of the forward scattered light intensities ofall cells (that is mature erythrocytes) included in the matureerythrocyte group 60.

Then, the body side controller 26 calculates and stores the IRF-Y andLFR-Y, as shown in FIG. 8 (step S6).

The IRF-Y is the average value of the forward scattered lightintensities of all cells (that is, juvenile reticulocytes) included inthe MFR range 68 and HFR range 70. The IRF-Y is a value which reflectsthe size and hemoglobin content of the juvenile reticulocytes.Accordingly, these values are useful for the differentiation andtreatment of anemia.

LFR-Y is the average value of the forward scattered light intensities ofall cells (that is, reticulocytes approaching mature erythrocytes)included in the LFR range 66. LFR-Y is a value which reflects the sizeand hemoglobin content of reticulocytes at the stage of differentiatingto erythrocytes. Accordingly, these values are effective in thedifferentiation and treatment of anemia.

Next, the body side controller 26 calculates and stores the number ofcells (mature erythrocytes) RBD-O included in the mature erythrocytegroup 60, the number of cells (reticulocytes) RET# included in thereticulocyte group 62, the percentage RET % of the number of cells(number of reticulocytes) included in the reticulocyte group 62 relativeto the total number of erythrocytes (number of matureerythrocytes+number of reticulocytes+fragmented erythrocytes), thenumber of cells (platelets) RLT-O included in the platelet group 64, thenumber of cells (fragmented erythrocytes) FRC# included in thefragmented erythrocyte group 63, and the percentage FRC % of the numberof cells (number of fragmented erythrocytes) included in the fragmentederythrocyte group 63 relative to the total number of erythrocytes (stepS7).

Then, the body side controller 26 calculates and stores the RET-He andRBC-He as component value from the RET-Y and RBC-Y calculation results,respectively, stored in step S5 (step S8).

RET-He is calculated using the following equation stored in the bodyside controller 26. RET-He is equivalent to the amount of hemoglobincontained in the reticulocytes.RET-He=A×exp (B×RET-Y)  Equation 1

-   -   (Where A=5.8439, and B=0.0098)

RBC-He is calculated using the following equation stored in the bodyside controller 26. RBC-He is equivalent to the amount of hemoglobincontained in mature erythrocytes, that is, MCH (mean corpuscularhemoglobin).RBC-He=C×exp (D×RBC-Y)  Equation 2

-   -   Where C=5.8439, and D=0.0098)

Then, the body side controller 26 calculates and stores the Delta-Hefrom the RET-He and RBC-He calculation results stored in step S8 (stepS9).

Delta-He is calculated by subtracting RBC-He from RET-He.

Then, the body side controller 26 transmits all data stored in steps S1through S9 to the terminal side controller 34 of the data processingterminal 2 (step S10).

Next, Then, the body side controller 26 ends the reticulocyte anderythrocyte analysis control routine, and starts the analysis controlfor the other clinical laboratory test items.

Equations 1 and 2 are determined by the following methods.

Equation 2 is obtained by analyzing a plurality of samples beforehand toacquire the forward scattered light intensity of mature erythrocytes(RBC-Y) and MCH (mean corpuscular hemoglobin), and plotting the analysisresults in a two-dimensional diagram, to determine the relationshipbetween RBC-Y and MCH.

The specific method of determining equation 2 is described below usingFIG. 11.

The vertical axis of the two-dimensional distribution shown in FIG. 11represents the magnitude of MCH, and the horizontal axis represents themagnitude of RBC-Y.

First, approximately 500 specimens were analyzed using the opticaldetection unit 20 to obtain the RBC-Y. The number of RBC (hereinafterreferred to as ‘RBC’) was then acquired for the same approximately 500specimens using the electrical detection unit 22, and subsequently theHGB concentration (hereinafter referred to as ‘HGB’) was acquired usingthe absorbance detection unit 24.

Then, the MCH was obtained from the acquired RBC and HGB using equation3 shown below.MCH=(HGB/RBC)×1000  Equation 3

Then the analysis results were plotted for these approximately 500samples, and a two-dimensional distribution diagram 160 was created.

The curve 162 was determined based on the sample distribution in thetwo-dimensional distribution diagram 160, and the equation representingthe curve was calculated. This equation is equation 2 described above,and is used to calculate MCH from RBC-Y.

Equation 1 is determined as described below.

RBC-Y is the average value of the forward scattered light intensities ofmature erythrocytes, and MCH is the amount of hemoglobin contained inthe mature erythrocytes. Since RET-Y is the average value of the forwardscattered light intensities of reticulocytes, if the same calculation ismade as the calculation of RBC-He using equation 2, a value can beobtained which is equivalent to the amount of hemoglobin contained inreticulocytes. Therefore, an equation having the same form as equation 2was used as equation 1 to calculate RET-He. Although MCH is essentiallythe amount of hemoglobin contained in red blood cells (including bothmature erythrocytes and reticulocytes), it is reasonable to consider MCHas the amount of hemoglobin contained in mature erythrocytes since thenumber of mature erythrocytes contained in peripheral blood is muchgreater than the number of reticulocytes.

Although equation 1 was determined by the method described above in thepresent embodiment, it is also possible to determine equation 1 byanalyzing a plurality of specimens beforehand to acquire the forwardscattered light intensity (RET-Y) of reticulocytes and the amount ofhemoglobin contained in reticulocytes, plotting a two-dimensionaldistribution diagram based on the analysis results, and determining anequation which represents the relationship between the RBC-Y and amountof hemoglobin contained in reticulocytes from the distribution conditionin the two-dimensional distribution diagram. The amount of hemoglobincontained in reticulocytes may be acquired, for example using a modelADVIA120 (Bayer Diagnostics, Inc.)

The screens displayed on the terminal side display 16 after the bodyside controller 26 ends the analysis for all clinical laboratory testitems is described below using FIGS. 9 and 10.

FIGS. 9 and 10 show the analysis result screens displayed on theterminal side display 16 after the body side controller 26 has completedthe analysis all clinical laboratory test items. FIG. 9 shows theanalysis result screen 71 a displayed when the main screen is selected,and FIG. 10 shows the analysis result screen 71 b displayed when theresearch screen (RBC related) is selected.

The analysis result screens 71 a and 71 b include an specimeninformation display unit 72 and an analysis result display unit 74.

The specimen information display unit 72 includes a specimen numberdisplay 102 for displaying the specimen number of the analyzed specimen(blood), a patient ID display 103 for displaying the identificaitonnumber of the patient from whom the analyzed specimen was collected,patient name display 104 for displaying the name of the patient, birthdate display 105 for displaying the birth date of the patient, sexdisplay 106 for displaying the sex of the patient, ward display 107 fordisplaying the ward to which the patient is admitted, attendingphysician display 108 for displaying the attending physician of thepatient, comment display 109 for displaying optional comments, assaydate display 110 for displaying the date the specimen was analyzed, andassay time display 111 for displaying the time at which the specimen wasassayed.

The analysis result display 74 includes a tag display 76, and a screencorresponding to the selected tag is displayed below the tag display 76.

The tag display 76 includes a main tag 114 for displaying the mainclinical laboratory test items, graph tag 116 for displaying all theobtained clinical laboratory test items, WBC tag 118 for displaying theclinical laboratory test items related to white blood cells, RBC tag 120for displaying the clinical laboratory test items related to red bloodcells, time series tag 122 for displaying the clinical laboratory testitems of specimens collected from a patient in time series, Q-flag tag124 for displays positive or negative, service tag 126 for displayingpredetermined service data, HPC tag 128 for displaying the HPC numberobtained by analyzing electrical signals output from the RF/DC detectorincluded in the electrical detection unit 22, research (WBC related) tag130 for displaying research items related to white blood cells, andresearch (RBC related) tag 132 for displaying research items related tored blood cells.

Since the main tag 114 is selected in the analysis result screen 71 ashown in FIG. 9, a main screen 101 is displayed which shows the mainclinical laboratory test items. The main screen 101 includes analysisdata displays 78 a and 78 b, and flag display 80.

The analysis data displays 78 a and 78 b include an item column 136,data column 138, unit column 140, and normal range column 142.

Names of clinical laboratory test items are displayed in the item column136, analysis results for each clinical laboratory test item aredisplayed in the data column 138, the units of the analysis resultsdisplayed in the data column 138 are shown in the unit column 140, andthe correlation of the analysis result of the analyzed specimen relativeto the normal range are displayed in the normal range column 142 (NRBC#and NRBC % are excluded). That is, the normal range column 142 displaysa lower limit bar 142 a representing the lower limit of the normalrange, an upper limit bar 142 b representing the upper limit of thenormal range, and an analysis result point 142 c is positioned so as tomake recognizable the correlation of the result with the normal rangeframed by the lower limit bar 142 a and upper limit bar 142 b.

Among the clinical laboratory test items displayed on the analysis datadisplays 78 a and 78 b, WBC, RET %, RET#, IRF, LFR, MFR, HFR, RET-He,NRBC#, NRBC %, NEUT#, LYMPH#, MONO#, EO#, BASO#, NEUT %, LYMPH %, MONO%, EO %, and BASO % are calculated using the optical detection unit 20.RBC, HCT, MCV, PLT, RDW-SD, RDW-CV, PDW, MPV, and P-LCR are calculatedusing the electrical detection unit 22. HGB is calculated using theabsorbance detection unit 24, MCH and MCHC are calculated using theelectrical detection unit 22 and absorbance detection unit 24, and PLTis calculated using the optical detection unit 20 or electricaldetection unit 22.

The flag display 80 includes WBC flag display 144 for displaying a flag(message indicating the analysis result is abnormal) related to WBC,RBC/RET flag display 146 for displaying flags relating to RBC and RET,and PLT flag display 148 for displaying flag related to PLT. In thescreen shown in FIG. 9, flags are not displayed in these flag displays.

RET-Y and RBC-Y are not displayed in the analysis result screen 71 a.

Since the research (RBC related) tag 132 is selected in the analysisresult screen 71 b shown in FIG. 10, the research (RBC related) screen151 is displayed as a screen including research items related to redblood cells.

The research (RBC related) screen 151 includes analysis data displays 82a, 82 b, 82 c, flag display 86, and scattergram/particle distributiondiagram display 88.

Names of clinical laboratory test items, analysis results for eachclinical laboratory test item and analysis units are displayed in theanalysis data displays 82 a, 82 b, 82 c. RBC, RBC-O, HGB, HCT, MCV, MCH,MCHC, RDW-SD, RDW-CV, PLT, PLT-I, PLT-O, PDW, MPV, P-LCR, PCT, RET#, RET%, IRF, LFR, MFR, HER, RET-He, RBC-He, D-He, RET-Y, RBC-Y, IRF-Y, RPI,FRC#, and FRC % are displayed on the analysis data displays 82 a, 82 b,and 82 c.

As previously mentioned, RBC-O is the number of cells included in themature erythrocyte group 60, and is an amount equivalent to the numberof mature erythrocytes. The sample analyzer of the present embodimentcalculates the number of erythrocytes RBC using the electrical detectionunit 22, and improves the reliability of analysis results by analyzingthe same clinical laboratory test items by two measurement principles.

RBC-He is the amount of hemoglobin contained in mature erythrocytes,that is, a value equivalent to MCH (mean corpuscular hemoglobin). Thesample analyzer of the present embodiment calculates MCH using theelectrical detection unit 22 and absorbance detection unit 24, andimproves reliability of analysis results by analyzing the same clinicallaboratory test items by two measurement principles.

PLT-I is the number of platelets calculated using the electricaldetection unit 22, and PLT-O is the number of cells contained in theplatelet group 64. Among PLT-I and PLT-O, reliability of analysisresults is improved by the more reliable higher value as the plateletnumber PLT.

D-He is the previously described Delta-He.

Since RET-He is a value equivalent to the amount of hemoglobin containedin reticulocytes, the unit pg, which expresses weight, is appended.Consequently, a user can easily comprehend that RET-He is a valueassociated with an amount.

Similarly, since RBC-He is a value equivalent to the amount ofhemoglobin contained in mature erythrocytes, the unit pg, whichexpresses weight, is appended. Consequently, a user can easilycomprehend that RBC-He is a value associated with an amount.

RPI is a value calculated from the analysis results of RET % and HCT (inthe present example, 0.75% and 42.4%), and can be used in evaluating thestatus of production of erythrocytes.

The scattergram/particle distribution diagram display 88 includesscattergrams 90, 92, 94, 96, and particle distribution diagrams 98 and100.

The scattergram 90 is an enlargement of only the region in which thelateral fluorescent light intensity is low among the scattergrams foranalyzing reticulocytes and mature erythrocytes; the forward scatteredlight intensity is plotted on the vertical axis, and the lateralfluorescent light intensity is plotted on the horizontal axis.

The scattergram 92 includes the regions in which the lateral fluorescentlight intensity is low and high in the aforesaid scattergram.

The scattergram 94 is an enlargement of the vicinity of the plateletregion in the aforesaid scattergram.

The scattergram 96 is a scattergram created using different assaysamples than those assay samples used for analyzing reticulocytes andmature erythrocytes in order to calculate NRBC# and NRBC %.

The particle distribution diagram 98 shows the erythrocyte distributioncreated using the electrical detection unit 22.

The particle distribution diagram 100 shows the platelet distributioncreated using the electrical detection unit 22.

The previously mentioned RBC and PLT-I are analysis results obtained byanalyzing these particle distribution diagrams.

As shown in FIGS. 9 and 10, RET-He, which is a component value, isdisplayed on the analysis result screen 71 a with the main clinicallaboratory test items, but RET-Y, which is the average value of theforward scattered light intensities of reticulocytes, is not. However,both RET-He and RET-Y are displayed on the analysis result screen 71 b.Consequently, this arrangement is useful since the user can quickly knowthe analysis results of the main clinical laboratory test items usingthe analysis result screen 71 a, and also see the analysis results ofdetailed clinical laboratory test items related to erythrocytes usingthe analysis result screen 71 b. These screens can be easily switchedusing tags.

The clinical significance of analyzing the amount of hemoglobincontained in reticulocytes is discussed below.

Iron-deficiency anemia and anemia occurring as a complication in casesof chronic disease (anemia of chronic disorder: ACD) are representativeexamples of anemia. Although administration of an iron-containingpreparation is very effective in treating iron-deficiency anemia, ironadministration is sometimes ineffective in treating ACD.

Accordingly, in treating anemia, iron-deficiency anemia and ACD must bedifferentiated. Managing the fluctuation in the amount of iron in theblood (ferrokinetics) is effective in making this differentiation.Clinical laboratory tests used in managing ferrokinetics includeclinical laboratory tests of serum iron, serum ferritin, solubletransferrin receptor (sTfR) and the like, however, these clinicallaboratory tests are not sufficiently sensitive and are expensive.

Since the amount of hemoglobin contained in reticulocytes reflects theiron content of the newly produced reticulocytes, analyzing this amountis effective in ferrokinetics management.

If RET-He is output using the sample analyzer of the present embodiment,a value is obtained which is equivalent to the amount of hemoglobincontained in reticulocytes, ferrokinetics can be managed quickly andinexpensively, and types of anemia can be effectively differentiated.

In recent years administration of recombinant human erythropoietin(rHuEPO) has become widely used as a treatment for renal anemia. Renalanemia is a disease caused by low production and secretion oferythropoietin by the kidneys.

Improvement often does not occur when treating renal anemia byadministering rHuEPO. Most frequently the cause is a functionaliron-deficient condition brought on by the administered rHuEPO. In suchcases iron-containing preparations must be administered in addition torHuEPO.

Accordingly, it is important to manage ferrokinetics when treating renalanemia, and analyzing the amount of hemoglobin contained inreticulocytes is effective in this regard.

In this case also, if RET-He is output using the sample analyzer of thepresent embodiment, a value is obtained which is equivalent to theamount of hemoglobin contained in reticulocytes, ferrokinetics can bemanaged quickly and inexpensively, and renal anemia can be effectivelytreated.

The Delta-He calculated by the sample analyzer of the present embodimentmay be used as an indicator for evaluating erythrocyte productionstatus, and is effective in differentiating and treating anemia.

The embodiment disclosed above has been described by way of examples inall aspects and is not to be considered as restrictive in any sense. Thescope of the present invention is expressed by the scope of the claimsand not by the description of the embodiment. The present invention maybe variously modified insofar as such modification is within the scopeand equivalences of the claims.

For example, although LFR-Y which is calculated in step S6 (refer toFIG. 4) is not displayed on the terminal side display 16 in the sampleanalyzer of the above embodiment, the present invention is not limitedto this arrangement inasmuch as LFR-Y also may be displayed on the bodyside display 11.

In the sample analyzer of the above embodiment, the body side controller26 may calculate the ratio of RET-Y and RBC-Y, and display the ratio onthe terminal side display 16. The ratio of RET-Y and RBC-Y may be usedas an indicator for evaluating the erythrocyte production status, and iseffective in the differentiation and treatment of anemia.

Although scattered light information is used to calculate valuesequivalent to contents of reticulocytes and erythrocytes, the presentinvention is not limited to this arrangement inasmuch as values whichare equivalent to the content of other cells, such as lymphocytes andmonocytes, also may be calculated and output.

In the sample analyzer of the present embodiment, the body sidecontroller 26 calculates the analysis results, and displays all analysisresults on the terminal side display 16, however, the present inventionis not limited to this arrangement inasmuch as all analysis results alsomay be displayed on the body side display 11, and the analysis resultsalso may be calculated by the terminal side controller 34.

Although the average value of the forward scattered light intensities ofreticulocytes and the average value of the forward scattered lightintensities of mature erythrocytes are used as scattered lightinformation in the sample analyzer of the above embodiment, the presentinvention is not limited to this arrangement inasmuch as the barycenteror mode value of the forward scattered light intensities of thereticulocytes and mature erythrocytes also may be used as scatteredlight information.

Scattergrams are created from the forward scattered light intensity andlateral fluorescent light intensity in the sample analyzer of the aboveembodiment, however, the present invention is not limited to thisarrangement inasmuch as scattergrams may be prepared from two types ofscattered light intensity (for example, forward scattered light andlateral scattered light), and scattergrams also may be prepared fromelectrical information (for example, current value, voltage value, andresistance value and the like) and scattered light intensity.

Although the sample analyzer of the above embodiment is provided with adevice body 1 and a data processing terminal 2, the present invention isnot limited to this arrangement inasmuch as the present invention isalso applicable to sample analyzers which incorporate the functionalityof the data processing terminal 2 in the device body 1.

Although the present invention is applied to a hemocytometer in theabove embodiment, the present invention is not limited to thisarrangement inasmuch as the present invention is also applicable toother sample analyzers, such as urine analyzers which analyze cellscontained in urine.

Although the present invention is applied to a sample analyzer in theabove embodiment, the present invention is not limited to thisarrangement inasmuch as the present invention is also applicable toprograms for controlling sample analyzers. Furthermore, the presentinvention is also applicable to computer readable recording media onwhich such programs are recorded.

1. A sample analyzer comprising: a detection unit for irradiating abiological sample with light and obtaining optical information; a cellclassification means for classifying cells contained in the biologicalsample into cell groups based on the optical information; a scatteredlight information obtaining means for obtaining scattered lightinformation relating to a cell included in a predetermined cell group; acalculation means for calculating a component value corresponding to anamount of component contained in cell included in the predetermined cellgroup based on the scattered light information; and an output device foroutputting the component value calculated by the calculation means. 2.The sample analyzer of claim 1, wherein the predetermined cell group isa reticulocyte group; and the calculation means calculates the componentvalue corresponding to an amount of hemoglobin contained in reticulocyteincluded in the reticulocyte group.
 3. The sample analyzer of claim 1,wherein the predetermined cell group is a mature erythrocyte group; andthe calculation means calculates the component value corresponding to anamount of hemoglobin contained in mature erythrocyte included in themature erythrocyte group.
 4. The sample analyzer of claim 1, wherein thepredetermined cell groups are a reticulocyte group and a matureerythrocyte group; and the calculation means calculates the componentvalue corresponding to an amount of hemoglobin contained in areticulocyte included in the reticulocyte group and the component valuecorresponding to an amount of hemoglobin contained in a matureerythrocyte included in the mature erythrocyte group, and furthercalculates the difference between these values.
 5. The sample analyzerof claim 1, wherein the scattered light information is calculated basedon the scattered light intensity of individual cells included in thepredetermined cell group.
 6. The sample analyzer of claim 5, wherein thescattered light information is an average value of the scattered lightintensities of individual cells.
 7. The sample analyzer of claim 1,further comprising: a memory for storing an operational expression forcalculating the component value from the scattered light information. 8.The sample analyzer of claim 7, wherein the operational expression is anequation created using the scattered light information obtainedbeforehand from a plurality of biological sample, and an amount ofcomponent contained in a predetermined cell obtained beforehand for theplurality of biological samples.
 9. The sample analyzer of claim 7,wherein the operational expression is represented by the followingequation;(component value)=A×exp(B×scattered light information) (where A and Bare constants)
 10. The sample analyzer of claim 1, wherein the detectionunit obtains the optical information by detecting scattered light andfluorescent light.
 11. The sample analyzer of claim 1, wherein theoutput device includes a display for displaying a screen which shows thecomponent value and a unit representing weight.
 12. The sample analyzerof claim 1 further comprising a means for obtaining the number of cellscontained in the predetermined cell group; and the output deviceincludes a display for displaying a screen which includes the componentvalue and the number of cells included in the predetermined cell group.13. The sample analyzer of claim 1, wherein the detection unit includesa flow cell through which passes a biological sample, a light source forirradiating the flow cell with light, and a detector for outputting asignal based on the intensity of light scattered in a forward directionby the irradiation of the biological sample passing through the flowcell with light.
 14. The sample analyzer of claim 2 further comprising ameans for obtaining the number of reticulocytes contained in thereticulocyte group; and the output device includes a display fordisplaying a screen which includes the number of reticulocytes and thecomponent value corresponding to an amount of hemoglobin contained inreticulocyte.
 15. The sample analyzer of claim 2, wherein the outputdevice includes a display for displaying a screen which includes thecomponent value corresponding to an amount of hemoglobin contained inreticulocyte, and reticulocyte group scattered light information, whichis scattered light information related to the reticulocyte group. 16.The sample analyzer of claim 2, wherein the output device includes adisplay capable of selectively displaying a first screen which includesthe component value corresponding to an amount of hemoglobin containedin reticulocyte and does not include reticulocyte group scattered lightinformation which is scattered light information related to thereticulocyte group, and a second screen which includes the componentvalue corresponding to an amount of hemoglobin contained in reticulocyteand the reticulocyte group scattered light information.
 17. The sampleanalyzer of claim 1, wherein the output device includes a display fordisplaying a screen for recognizing the correlation between thecomponent value and a normal range.
 18. A sample analyzer comprising: adetection unit for irradiating a blood sample with light and obtainingscattered light information and fluorescent light information; a cellclassification means for classifying cells contained in the blood sampleinto a plurality of cell groups including a reticulocyte group based onthe scattered light information and fluorescent light informationobtained by the detection unit; a reticulocyte group scattered lightinformation obtaining means for obtaining reticulocyte group scatteredlight information relating to a reticulocyte included in thereticulocyte group; a calculation means for calculating an amount ofhemoglobin contained in the reticulocyte based on the reticulocyte groupscattered light information; and a display for displaying the amount ofhemoglobin calculated by the calculation means.
 19. A computer programproduct for executing a method of analyzing a biological sample, thecomputer program product comprising: computer program code for obtainingoptical information from a biological sample irradiated with light;computer program code for classifying cells contained in the biologicalsample into a plurality of cell groups based on the optical information;computer program code for obtaining scattered light information relatingto a cell included in a predetermined cell group; computer program codefor calculating a component value corresponding to an amount of acomponent contained in a cell included in the predetermined cell groupbased on the scattered light information; and computer program code foroutputting the calculated component value.
 20. The computer programproduct of claim 19, wherein the predetermined cell group is areticulocyte group; and the computer program code for calculatingcalculating the component value corresponding to an amount of hemoglobincontained in reticulocyte included in the reticulocyte group.